Figure 1

miRNA biogenesis and inhibition of miRNA function by antimiR oligonucleotides. miRNA genes are transcribed by RNA polymerase II into long primary miRNA transcripts, termed pri-miRNAs that are usually several kilobases long and possess a 5' CAP and a poly(A) tail. Pri-miRNAs are processed in the nucleus to ~70 nt pre-miRNAs by the nuclear Microprocessor complex, consisting of DGCR8 and the RNase III enzyme Drosha. Pre-miRNAs are exported to the cytoplasm by Exportin-5 and processed further by Dicer, to ~22 nt double-stranded miRNA duplexes that are loaded into an Argonaute protein in the miRISC and rapidly unwound. During this process the mature miRNA is retained in the miRISC, whereas the complementary strand, known as the miRNA star (miR*) is released. Metazoan miRNAs guide the miRISC to partially complementary sites in the 3' UTRs of target mRNAs to promote their translational repression or deadenylation and degradation. Chemically modified antimiR oligonucleotides sequester the mature miRNA in competition with cellular target mRNAs leading to functional inhibition of the miRNA and derepression of the direct targets.